ASTRO 2019: SBRT After Disease Progression on Immunotherapy Increases PFS in Patients With Metastatic NSCLC

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Non–small cell lung cancer (NSCLC) accounts for the vast majority of all lung cancers—between 80% and 85% of those diagnosed in the United States—and is among the most deadly cancers for both men and women, exceeding the mortality rate of colon, breast, and pancreatic cancers combined.

The results from a phase II study by Campbell et al indicate that some patients with advanced-stage NSCLC may benefit from treatment with stereotactic body radiotherapy (SBRT) following disease progression on the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab. The improvement in progression-free survival (PFS) is associated with a boost in CD8 T-cell activity after the combination therapy. The study was presented at the 61st Annual Meeting of the American Society for Radiation Oncology (ASTRO) and simultaneously published in the International Journal of Radiation Oncology · Biology · Physics.

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Study Methodology

The researchers enrolled 56 patients diagnosed with NSCLC into the trial, all of whom had two or more measurable lesions at enrollment. Histologic analysis of biopsy samples was performed at enrollment, and the number of tumor-infiltrating lymphocytes (TILs) was given a qualitative score between 0 and 3. If patients had progressed on prior anti–PD-1 therapy at the time of enrollment, they received SBRT upfront and continued on pembrolizumab. The systemic response to radiotherapy was evaluated using RECIST v 1.1 criteria (with omission of the radiated lesion). The overall response rate after SBRT was defined as the percentage of patients achieving a complete response or partial response, and the disease control rate was defined as the percentage of patients achieving a complete or partial response or stable disease. Adverse events were measured using the common terminology criteria for adverse events (CTCAE) version 4. Mass cytometry by time-of-flight was performed on the peripheral blood of a subset of patients.


Of the 56 patients enrolled in the phase II study, 50 were immunotherapy-naive and began pembrolizumab on the trial. Of these 50 patients, 16 experienced disease progression and were deemed suitable candidates for SBRT. Six patients had progressed on anti–PD-1 therapy at enrollment and received SBRT upfront. Of the 22 patients allocated to SBRT, 21 completed treatment.


  • Patients who received high-dose radiation following immunotherapy lived, on average, 5 months longer without additional disease progression.
  • Tumors outside the radiation-treated area shrank by 30% or more in 2 patients and 10 patients experienced disease stabilization following the addition of radiotherapy.

The addition of SBRT to pembrolizumab resulted in a mean of 150.67 days before further disease progression. The disease control rate was 57.14%. There were 2 patients (9.52%) who achieved a partial response which was sustained for more than 1 year, and 10 patients (47.62%) who achieved stable disease after SBRT. Patients with elevated TIL scores (2–3) showed improved PFS when compared with patients that had lower TIL scores (0–1), with a mean of 215 vs 59 days, respectively. Patients who reported an immune-related adverse event survived longer than patients with no immune-related adverse event, with a mean of 208 days vs 88 days, respectively. Mass cytometry by time-of-flight analysis showed patients with a systemic partial response after SBRT had a population of CD8-postive, CD127-negative, Ki-67–positive, CD45RO-positive T cells that correlated with response.

“The addition of SBRT after progression on immunotherapy resulted in increased PFS, a systemic response rate of 9.52%, and a disease control rate of 57.14%. Improved PFS correlated with an increased TIL score, the presence of an immune-related adverse event, and T-cell activation status,” concluded the study authors.

Clinical Relevance

“We are starting to see that the combination of immunotherapy and radiation is safe and there are some hints that for certain patients, radiation might be an important option when immunotherapy no longer curbs disease progression,” said lead study author Allison M. Campbell, MD, PhD, of Yale New Haven Hospital, in a statement. “Our study lays the groundwork for a phase III randomized trial, which is the gold standard for changing guidelines and clinical practice.”

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